Using the Cell-Cycle Risk Score to Predict the Benefit of Androgen-Deprivation Therapy Added to Radiation Therapy in Patients With Newly Diagnosed Prostate Cancer.

ABSTRACT

PURPOSE: Guidelines recommend adding androgen-deprivation therapy (ADT) to radiation therapy (RT) in certain patients with localized prostate cancer. Individualized genomic testing may improve the prognostic accuracy of risk assessments. Herein, we describe a mathematical model of the benefit of adding ADT to RT as a function of the personalized clinical cell-cycle risk (CCR) score to inform 10-year metastasis risk. METHODS: A model of absolute risk reduction (ARR) was built using a retrospective cohort of men tested with Prolaris who received RT alone (N = 467). The relative benefit of ADT added to RT to reduce distant metastasis was estimated at 41% on the basis of a meta-analysis of randomized trials. The ARR and number needed to treat (NNT) were computationally derived in patients clinically tested with Prolaris between January 1, 2020, and October 31, 2022 (N = 56,485). Risks were predicted using a cause-specific Cox proportional hazards model with CCR score predicting time to metastasis. A CCR score of 2.112 represents the validated multimodal treatment (MMT) threshold. RESULTS: The ARR from ADT increased from almost zero at low CCR scores to 17.1% at CCR = 3.690 with the corresponding NNT = 6, indicating that adding ADT to RT would prevent metastasis within 10 years for one of every six treated individuals. In the clinical cohort, the average ARR was 0.86% in individuals under the MMT threshold (NNT = 116). The average ARR was 8.19% in individuals above the MMT threshold (NNT = 12). Broad ranges of ADT benefit were observed within National Comprehensive Cancer Network risk categories. CONCLUSION: The precise and personalized risk estimate of metastasis provided by the CCR score can help inform patients and physicians when considering treatment intensification.